Antibody dependent cell cytotoxicity (ADK) appears to comprise an effective means of tumor destruction both in vitro and in vivo . However, the potential role of ADK in protection against human tumors has not been comprehensively explored. In this application we propose to use reagents we have developed, and which have been made available to our laboratory, to systematically examine ADK of lymphoma cells (LC). We have prepared or obtained monoclonal antibodies (MAb) to each of the known human myeloid Fc receptors, to a variety of human myeloid cell surface antigens and to lymphoma cells. We propose to use these MAbs to prepare heteroantibodies which would link human leukocytes to tumor target cells as the basic for a detailed study of the potential role of ADK in the therapy of lymphoma. In particular, we would use these heteroantibodies as mediators of cytotoxicity: to determine the role of the different Fc recptors for IgG and other myeloid cell surface markers in ADK of LC; to examine the ability of monocytes, macrophages, and neutrophils to kill lymphoma cells though different Fc receptor; to study the role of antigen modulation on ADK of LC; to investigate the modulation of cellular killing mechanisms by interferons and other factors as well as the effects of mediators on the susceptibility of LC to killing; and to evaluate the possibility that an impairment of cytotoxicity exits in effector cells from patients with lymphoma. In addition we would use a model system in a supplemental approach to facilitate specific analysis of the role of antigen density and LC susceptibility in ADK. These studies would provide valuable information on ADK as it relates to the killing of lymphoma cells, a clearer understanding of the potential of heteroantibodies in cell mediated cytotoxicity and would provide data useful for the development of other immunologic approaches to the treatment of human tumors.